This application is for the Continuation of the Virginia Mason Medical Center (VMMC) Clinical Site and its Subsites of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). Nonalcoholic fatty liver disease (NAFLD) affects one out of every three adults and five children in North America and is a growing public health issue in the United States. NAFLD, and especially nonalcoholic steatohepatitis (NASH), may lead to end-stage liver disease and primary liver cancer, as well as liver-, cardiovascular-, and cancer-related mortality, resulting in major increases in health burdens and costs. The NASH CRN is ideally and uniquely positioned to impact the growing public health significance of NASH that can only be addressed via a large research consortium. The primary objective of the NASH CRN is to perform clinical research on NASH and NAFLD in adults and children. A closely linked and high priority secondary objective is to conduct translational research in NASH and NAFLD focusing on the pathogenesis that will provide the basis for understanding the natural history and developing means of better diagnosis, treatment, and clinical management. In the next phase of the NASH CRN, the adult and pediatric therapeutic trials initiated during the previous funding cycle will be completed, and new therapeutic trials, including phase 2a proof of mechanism and phase 2b clinical trials will be initiated, to develop evidence-based treatment options that are safe, effective, simple, and inexpensive. The longitudinal cohort of adults and children with NAFLD will be extended, which will prospectively define the natural history of the disease, the cardiovascular and metabolic risk factors, and will aid in biomarker discovery and validation, and development and validation of non-invasive techniques to evaluate and identify those with NASH/NAFLD, who will respond, and how quickly the disease is progressing. VMMC has played a leading role in both the clinical and translational research success of the NASH CRN since the inception. VMMC was a leading enrolling site in both the PIVENS and FLINT trials. VMMC currently has 5 ongoing NASH CRN approved ancillary studies, including AS40, The Role of Iron Pathogenesis of NAFLD (R01DK087696), which has made major contributions toward understanding the effect of iron in NAFLD. VMMC investigators have contributed 20 presentations at national and international scientific meetings and coauthored 14 manuscripts on behalf of the NASH CRN. The NASH CRN is poised to continue its major impact on the field and directly advance the mission of the National Institutes of Health to improve the health of the public.